Four simple rules that are sufficient to generate the mammalian blastocyst
Fig 1
Schematic of the early embryonic development.
The zygote (embryonic day [E] 0.5) undergoes 3 rounds of cleavage divisions, resulting in 8 cells at E2.5. During the next round of division, the blastomeres undergo compaction and become polarized, resulting in the outer trophectoderm (TE) (blue) and the inner cell mass (ICM) (still coexpressing Gata6 and Nanog). The TE expresses the transcription factor caudal-related homeobox 2 (Cdx2). At E3.5, a cavity has formed, and the ICM is positioned at 1 side of the embryo. At this stage, the ICM transcription factors, Gata6 (red) and Nanog (green), are expressed in a mutually exclusive salt-and-pepper pattern in some cells. At E4.5, Nanog- and Gata6-expressing cells have physically segregated into 2 distinct layers and are developmentally restricted to either the epiblast (EPI) or primitive endoderm (PrE). The lower panel shows immunostaining of embryos at different stages during preimplantation development. Color coding is the same as in the panel above. The timing of the 4 different rules that we apply is indicated on top of the diagram.